The cardiovascular system is mostly controlled by the autonomic nervous system (ANS) through complex interplay between the vagal and sympathetic divisions (Guyton and Hall 2006). The ANS establishes and maintains a dynamic adaptive state, allowing an organism to respond to internal and external demands. It mediates changes in HR, blood pressure and peripheral vascular tone in response to daily challenges, including change of posture and physical exercise. A large body of evidence has shown that the functioning of the ANS plays a substantial role in cardiovascular health and disease (e.g. Rosenwinkel et al. 2001; Carter et al. 2003; Harris and Matthews 2004)
One model of stress was developed by Folkman et al. (1986) which identifies two processes: cognitive appraisal and coping. When faced with a possibly hazardous encounter with the environment, the person will go through the process of cognitive appraisal, evaluating the possible outcome of this encounter. Coping is defined here as the process of dealing with stress, in which the person changes the environment or her own internal expectations in order for these to match, or for the environment to exceed her expectations.
Stress is the body's multi-system response to any challenge that overwhelms, or is judged likely to overwhelm, selective homeostatic response mechanisms (Trevor A Day 2005). According to Lazarus, stress is defined as an internal process that occurs when a person is faced with a demand that is perceived to exceed the resources available to effectively respond to it, and where failure to effectively deal with the demand has important undesirable consequences (Lazarus et al, 1984). When under stress, the body responds in a way similar to how it responds to danger. Fatigue, being generally ill and feeling jittery are all sensations of stress (Selye, 1984).
One framework for studying stress is the Demand-Control-Support model (Karasek & Theorell 1990). This model, created with a focus on work-related stress, examines the relationship between the individual and the environment, from the point of view of the individual. Karasek & Theorell propose three factors to define the perception of the work environment: demand, control and support. Demand is the amount of workload placed on the person. Control refers to autonomy i.e. whether the individual is able to decide how to complete the work tasks or not. Support is defined as the amount of assistance that the worker gets from the manager or supervisor. This model is important in the context of research in effects of long-term stress (SALTSA 2006). Individuals with high demand, low control and low support usually experience prolonged periods of stress (Karasek & Theorell 1990).
A stress experience can be measured using three methods: evaluating the stimuli, evaluating the subjective cognitive response (by asking the subject how he feels) or evaluating the physiological bodily responses. The first method can obviously only be applied with humans and can potentially be deceiving because it does not take into account the capabilities of the subject to deal with the stressor. The second measurement method can be very subjective (Ursin & Eriksen 2004). Both are normally difficult to measure in real-time.
There are two primary physiological stress reaction systems: The hypothalamus-pituitary-adrenal (HPA) system and the autonomic nervous system (ANS). HPA and ANS play key roles in mediating this multisystem response. The ANS, including both the parasympathetic and sympathetic pathways, is highly responsible for this regulation of homeostasis (Porges 1992). Prolonged stress response may manifest itself in three forms: anticipatory responses to potential stressors, slow recovery from stressors, and/or recurrent activity related to past stressors (Brosschot et al. 2005).
The human stress response involves a complex signaling pathway among neurons and somatic cells. The internal environment of the body is regulated by two control systems: neuronal and hormonal (Jänig 2003). In stress research, two hormonal axes are often referred to: sympathetic-adrenal-medullary axis and hypothalamic-pituitary-adrenocortical (HPA) axis. Both of these axes involve adrenal glands, the medulla in former and the cortex in latter. The medulla is activated by the sympathetic branch of the ANS and its products are adrenaline and noradrenaline, common catecholamines. The product of the cortex is a group of hormones known as the corticosteroids, and perhaps the most important of these is cortisol. The HPA axis comprises the system of feedback interactions among the hypothalamus, pituitary gland, and adrenal glands. The HPA axis is a major part of the neuroendocrine system that controls reactions to stress and regulates many body processes, including digestion, the immune system, mood and emotions, sexuality and energy storage and expenditure.
Neuronal regulation acts rapidly and is mediated by the ANS. ANS is a part of the nervous system composed by a complex net of nerves that are distributed throughout the body and directly control the function of most tissues and organs. The ANS is mostly responsible for involuntary and non-conscious functions like regulating the HR, blood pressure, respiration, sweating and the like. Hormonal regulation is in general slower than the neuronal regulation (Jänig 2003). Both ANS and HPA work in conjunction to maintain the body in an equilibrium situation, also known as homeostasis, a concept created in 1865 by Claude Bernard that can be described as a slow regulatory process that operates on an organism, maintaining it in a stable condition (Cannon 1932).
A concept of allostatis defined by Sterling & Eyer (1988) is similar to homeostasis but it works faster. It responds to rapid changes in the environment, such as exposure to a pathogenic (e.g. virus or bacteria), or a prolonged “fight or flight” reaction. Every time there is a stress response, the organism enters a state of arousal and each internal system responds to adapt to the change. This response starts in the brain, with the activation of the Sympathetic system and deactivation of the Parasympathetic system from the ANS occurring in parallel with a release of hormones in the HPA. This response has short-term benefits as it adapts the organism to the environment. However, it does not come without long-term consequences. Either because of inefficient responses or repeated exposure to stressors, allostasis has a long-term effect on the body called allostatic load.
Further, McEwen & Wingfield (2003) define two types of allostatic load:
Type 1 allostatic overload occurs when energy demand exceeds supply, resulting in activation of the emergency life history stage. This serves to direct the animal away from normal life history stages into a survival mode that decreases allostatic load and regains positive energy balance. The normal life cycle can be resumed when the perturbation passes. Type 2 allostatic overload begins when there is sufficient or even excess energy consumption accompanied by social conflict and other types of social dysfunction. The latter is the case in human society and certain situations affecting animals in captivity. If allostatic load is chronically high, then pathologies develop. Type 2 allostatic overload does not trigger an escape response, and can only be counteracted through learning and changes in the social structure.
Various studies show that allostatic load can lead to permanent changes in immunological, cardiovascular and neuronal systems. Stress has been associated with infections and inflammations, cardiovascular, pulmonary, dermatological and immunitary diseases, diabetes, obesity, psychiatric conditions, and progression to cancer (e.g., Seeman et al. 1997, McEwen 1998, McEwen & Wingfield 2003, Kaplan et al. 1991, Yun & Doux 2007). Increased cardiovascular risk seems to be related with over activity of the Sympathetic nervous system (Julius 1993), due to frequent activation in stress responses. It has been shown that stress impairs the homeostatic regulations of the body, particularly the cardiovascular regulation (Mezzacappa et al. 2001, Lucini et al. 2005). The reduced autonomic regulation of the heart makes it more vulnerable to acute stress (i.e. stress happening during short periods of time), where short term rises in HR and blood pressure can cause arrhythmia and sudden death (Lucini et al. 2005).
Both the sympathetic branch of the ANS and the HPA axis are activated during the acute stress. Chronic and/or unpredictable activation of these stress response systems can lead to a diminished capability to respond appropriately. Increased activation of the HPA axis and that of the sympathetic nervous system are frequently reported in depressed and anxious patients.
The phenomenon of beat-to-beat fluctuation of HR has been termed respiratory sinus arrhythmia. During recent decades, a variety of HRV methods have been developed and their ability to evaluate the cardiac autonomic modulation has been proven in multiple situations, as well as under influence of different stressors. The measurement of HRV provides a non-invasive tool for assessing autonomic HR control.
HRV is a term used to describe the variations in time-intervals between heart beats, i.e. variations in electrocardiographic R-to-R peak interval (RRI) lengths. HRV is primarily due to the changing modulations of vagal and sympathetic control of the heart and may therefore be considered as an estimate of autonomic HR control. Methods for detecting beats can be: Electrocardiography (ECG), blood pressure, ballistocardiograms, and the pulse wave signal derived from a photoplethysmograph (PPG). Detection of beat-to-beat interval and subsequent measurement of the HRV can also be performed by optical measurement using infra-red light emitting diodes (LED)'s. IR LED's are used to measure either transmittance or reflectance of light through body tissue such as tip of the finger or ear lobe or elsewhere on the body.
Finger plethysmography (FPG) is a simple, noninvasive, well-known method for monitoring peripheral circulation. Peripheral blood vessels contain a high concentration of arteriovenous anastomosis, innervated by alpha-adrenergic nerve fibers. Peripheral blood flow thus reflects ANS activity, which is commonly known as one indicator of mental stress. Although indices of ANS activity are usually calculated using HRV, a number of recent reports have noted that finger pulse rate variability has nearly the same physiological function as HRV. Because measurement of HRV usually requires electrodes to be attached to the chest or stomach, and electrodes sometime pick up noise from body movements, FPG is a superior method of measuring acute mental stress. It is a minimum burden on user and it can accurately measure changes in peripheral blood flow. Furthermore, it has been proposed that the FPG waveform reflects health conditions, with the signal becoming simpler and weaker as a result of disease or aging. Studies show that peripheral arterial vasoconstriction induced by mental stress predicts stress-induced myocardial ischemia. Also acute mental stress will lead to sympathetic nervous system activation and consequent peripheral vasoconstriction. Chronic stress may lead to peripheral blood ischemia and, consequently, cardiovascular disease. Measuring FPG during stress is important as a means of predicting health outcomes.
A modified HRV has been proven to be associated with medical conditions such as acute and chronic stress, recovery from stress or physical loading, congestive heart failure, diabetic neuropathy, depression, post-cardiac transplant, and poor survival in premature babies. HRV is a key marker of autonomic dysfunction and the effects seen through it are immediate, while blood pressure, baroreflex, and therapeutic effects are delayed. This is consistent with data on the relationship among stress, HPA axis activity, and brain function.
The effects of stress and recovery influence the resources of the ANS. Under optimal conditions, the autonomic resources are fully recovered and mainly vagal resources are needed. Typically however, the resources are not fully recovered, but there is no risk of problems in case of disposition to stress. If the resources are low, the risk of problems in autonomic modulation increases, as the sympathetic activation is increased already during rest. In the case of chronic exhaustion the resources are very small, and mainly sympathetic.
The tenth cranial or vagus nerve is responsible for the vagal (parasympathetic) modulation of heart (Hainsworth 1998). Activity in the vagal nerves slows the HR by slowing the rate of spontaneous depolarization of pacemaker cells. At rest, HR decreases from the intrinsic value of 110-120 bpm to 60-80 bpm by the predominance of vagal activity over sympathetic activity. The balance between vagal and sympathetic activity is responsible for adjusting the HR. HR values lower than the intrinsic values indicate vagal predominance while HR values over intrinsic values reflect sympathetic predominance (Hainsworth 1998).
Increase in sympathetic activity increases HR by increasing the rate of depolarization of pacemaker cells. Whereas vagal activity can delay the very next heart beat, sympathetic responses are much slower. Maximal responses may not occur for as long as 20-30 seconds. Similarly to the vagal effects, the interval between depolarizations, R to R interval (RRI) is more closely related to the frequency of sympathetic stimulus. High sympathetic drive is responsible for the high HRs seen during maximal exercise, also increasing the force of contraction and shortening the duration of systole.
Decreased vagal function and HRV are shown to be associated with increased fasting glucose and hemoglobin A1c levels, increased overnight urinary cortisol, and increased proinflammatory cytokines and acute-phase proteins. All of these factors have been associated with increased allostatic load and poor health. Thus, vagal activity appears to play an inhibitory function in the regulation of allostatic systems. The prefrontal cortex and the amygdala are important central nervous system structures linked to the regulation of these allostatic systems via the vagus nerve.
While the changes in e.g. blood pressure and HR are the result of combined changes in parasympathetic and sympathetic nervous system (PNS and SNS respectively), HRV indicates individual contributions of PNS and SNS. Beat-to-beat variability in HR or “instantaneous HR” is governed by modulations in SNS and PNS activity. HR oscillates with many frequencies that reflects the influence of different blood pressure systems: rapid fluctuations (HF, 0.4-0.15 Hz) are caused by vagal activity, slow fluctuations (LF, 0.15-0.04 Hz) are caused by a mixture of sympathetic and vagal activity, slower fluctuations are caused by even slower regulatory systems (e.g. temperature fluctuations, day-night periodicity).
HRV is most commonly analyzed with time domain and conventional frequency domain methods. Time domain analysis can be easily calculated with simple statistical methods. The simplest index is the standard deviation of the RRIs over the selected period (SDNN). Frequency domain analysis decomposes the RRI data into its frequency components and quantifies them in their relative intensity, termed power. It provides information how overall HRV is distributed as a function of frequency. E.g. nonparametric Fast Fourier Transformation and parametric autoregressive modeling are used. The advantages of the nonparametric methods are the simplicity of the algorithm and high processing speed, while the advantages of parametric methods are smoother spectral components, simple post-processing with an automatic calculation of different components and an accurate estimation of power spectral density, even on small number of samples.
HRV has classically been used to assess autonomic HR control at rest. A conventional frequency domain analysis of HRV has been developed essentially for conditions in which the level of HR is unchanged. Recently, studies have been targeted at developing novel methods of HRV analysis that allow the assessment of HRV also in conditions when HR changes rapidly. By using time-frequency approaches it is possible to obtain information on autonomic control when HR changes rapidly. Time-frequency analysis and a short-time Fourier transform (STFT) method allows HRV also to be assessed from non-stationary signals. This is a major advantage, since autonomic HR control is characterized by transient changes.
Most real-life challenges induce a rapid increase or decrease in HR. It has been recognized that transient changes in HR in response to variety of tasks reveal important information on the functioning of the ANS. In order to obtain information on autonomic control during strongly time-dependent phases of an intervention, several tools for time-frequency analysis have been applied to RRI data. The advantages of the STFT method are computational efficiency, simple implementation and automaticity. It can also be seen as an objective method as after the selection of window length and frequency ranges no further decisions are needed. The STFT method calculates consecutive power spectra of short portions (of constant duration) of the signal and thus informs about changes in the power spectrum as a function of time.
Measuring the sympatho-vagal balance utilising HR and HRV offers deep understanding of dynamic, autonomic interrelations in humans in totally noninvasive, unobtrusive means. When instantaneous balance between sympathetic and vagal nerve activities i.e. sympathovagal balance and modulation are measured dynamically in every day measurable life events it is possible to generate great understanding and long term view and trend on the persons bodily reactions in different daily life situations.
When combined and correlated with the measurement of activity i.e., the measured level of physical provocation or non-provocation (i.e., the situation where there is not physical activity e.g., mental load or pressure) it is possible to create multidimensional view on the personal healthy area in the context of ANS reactions in ratio to the activity level of the user in different measurable situations.
In addition to associations with age, gender and physical fitness, several studies show great inter-individual variation in HRV indices. It should also be noted that heritable factors may explain a substantial proportion of variation in HR and HRV. HRV indices, with the exception of the LF/HF ratio, are independent of body position and rather stable when repeated on the same day, and they should be used when studying long-term observations of autonomic measurements in healthy subjects.
Stressful conditions and prolonged exposure to stress can manifest themselves into a number of emotional, cognitive, physiological and somatic symptoms (Melamed et al., 2006). There are a large number of investigations dealing with HRV during exposure to standardized psychological stressors such as mental arithmetic. Vagal modulation of the heart appears to be sensitive to recent experiences of persistent emotional stress regardless of age, gender, respiration rate or cardio-respiratory fitness. Chronic work stress (high effort-low reward) has been associated to low HRV during work, leisure and sleep both during work days and weekends. Psychosocial stress symptoms during the workday may not be harmful for the health, but if prolonged, they may lead to cardiovascular disease.
In recent years, laboratory research on mental workload and stress reactivity has shown that certain psychologically relevant measurable biochemical and physiological indices provide additional measures to assess and monitor our adaptation resources. When these bodily reactions are evaluated in real-life conditions as well, it offers a useful way of examining one's reactions to stress and recovery in more practical settings. Vagal modulation of heart appears to be sensitive to recent experiences of persistent emotional stress regardless of age, gender, respiration rate or cardiorespiratory fitness. The results of academic studies have shown that higher incidence of stress symptoms are significantly associated with lower HRV in the orthostatic test regardless of age and gender. Also it has been shown that HRV measurements are useful tools in analyzing stress in real-life conditions together with subjective evaluations of stress.
Stress results primarily from unmanaged emotions. Factors such as anxiety, worry or fear are disablers of performance. States of peak performance have a measurable physiological correlate. A physiological state characterized by improved and coherent heart rhythm leads to measurable improvement in mental and cognitive performance, including heightened decision-making. Different emotions, e.g. levels of hostility have been shown to affect HRV. Different techniques that engender positive thought processes in individuals have been demonstrated to produce a significant improvement in HRV. Emotions such as hostility and anger produce a sympathetically dominated HRV, whereas feelings of appreciation shift the HRV power spectrum in the opposite direction. It has been shown that people who express positive emotions show less life stress and are less likely to become ill.
A physiological state of entrainment, where HRV patterns, brain activity and respiration synchronize with each other, correlates with a state of peak performance. This same state is also associated with a reduction in stress-related symptoms, including tachycardia, tension and various aches and pains. These positive effects are best achieved during conditions of positive emotional management. There is now increasing evidence that the physical symptoms of stress are linked negatively to workplace effectiveness. Techniques that improve HRV in individuals have been shown to benefit organizations by increasing productivity, reducing health care costs, lowering absenteeism and improving retention. Also studies have shown that executives with stage 1 and 2 hypertension have been able to restore their blood pressure to normal without medication, by learning techniques that regulate their HRV.
The role of mood, emotions and thought processes (positivity and negativity) are often ignored or placed in the background when addressing an individual's well-being and recovery process. More recent research, particularly involving HRV, is demonstrating the profound potential gain that can be achieved on the basic physiological regulatory processes that govern health by addressing an individual's emotional response and employing simple techniques to alter the negative thought processes that affect our responses to challenge and stress. HRV is a great tool by which we can examine the interface and coherence between mind and body. An ability to control HRV could well alleviate negative mood states in people seeking assistance for inadequate stress responses, anxiety or depression. Since there is a clear association between negative mood states and heart disease, the efficacy of any psychological intervention to reduce the risk of heart disease would be improved if it focused directly on improving ANS imbalance characterized by SNS dominance and low HRV. Also, since an increasing number of physical ailments appear to be associated with ANS imbalance the potential application of HRV to monitor this balance is enormous.
In addition to the passive head-up tilt, the Active Orthostatic Task (AOT) is a simple non-invasive test that provokes well-documented abrupt cardiovascular changes, eliciting a fast response in the different divisions of the autonomic nervous system. For example, unaided standing up after sitting down for some time (for a few minutes) and remaining standing for a short time (e.g., 1 min) is an AOT. This kind of an AOT results in a shift of blood away from the chest to the venous system below the diaphragm, and thus arterial blood pressure decreases rapidly. In normal subjects, compensatory mechanisms are activated immediately after standing-up in order to maintain arterial blood pressure at an appropriate level of perfusion for all the vital organs, especially the brain. The initial adjustments to standing-up are primarily mediated by the autonomic nervous system, and the humoral regulatory system only becomes involved during prolonged standing. Studies show that the fast and slow cardiac response to the AOT seems to be mediated by the vagal system alone. An example of the opposite kind of AOT is sitting down after standing or walking. The short-time Fourier transform (STFT) method to analyze HRV data is successfully used to detect vagal response to the AOT.
HR and HRV measured as a part of orthostatic tests can be used to predict with high level of accuracy the chronic stress that a person is going through. Orthostatic tests include measuring various vital parameters of the body while the person is supine or sitting and relaxed for several minutes and while person stands up and is standing in an upright position for some time. The change from lying to standing position creates redistribution of blood volume. Systolic blood pressure decreases and HR increases. The peak HR is found approximately 15 seconds after standing up. Being in a continued standing up position, HR starts to oscillate at a certain level. The orthostatic HR is the difference between the HRs at supine rest and at standing positions. For example, if the average HR in a lying position is 56 and at standing 80, the orthostatic HR is 24 beats per minute (bpm).
However, many different stages can be used to measure the standing HR. For example, few health care providers prefer using the peak HR after the person stands up and others prefer using the average HR after the HR has peaked. The peak HR is usually interpreted to reflect parasympathetic nervous activity and the average HR to reflect sympathetic activity, although both these parameters are indicators of disturbances in ANS.
Since precise instructions for performing the orthostatic test do not exist, the patients are typically advised to decide a practice for themselves and then perform the test always the same way. Therefore, to perform the test the person needs to especially designate a time during the day when he has to remain in a supine or sitting position for X minutes and measure the resting HR. Thereafter, he/she has to stand up and then measure the average HR or the peak HR as advised.
Several measurements of the orthostatic HR need to be performed at plurality of times in a day over a period of several days before a stress level can be derived conclusively. Thus, orthostatic HR measurement may prove to be a tedious task for working professionals having busy work schedules. The cumbersome measurement procedure ultimately leads to missed test readings or tests performed without following the protocol properly, thereby resulting in inconclusiveness of the readings obtained.